had baseet al. had baseline HBV infection and 8.4 had baseline HCV infection, compared with 12 and 30 for HBV and HCV, respectively, in the SHARP trial. A-674563 There has been some evidence that patients with HBV associated HCC may have worse prognosis that those with HCV related HCC and others which suggests sorafenib may be less efficacious in HBV patients. A subset analysis of their patients with HBV infection showed that those treated with sorafenib had longer OS and TTP than those given placebo, and another study showed that the safety profile of sorafenib in HBV patients was similar to the overall study population, leading the authors to conclude that sorafenib is just as efficacious in HBV patients. Subgroup analysis of patients with HCV in the SHARP study showed similar safety profile in the 178 patients with HCV compared to the overall population.
Adverse events were mostly predictable and manageable. OS and TTP in this subset of patients were similar to those of the overall study population. These findings support the efficacy and safety results reported in the SHARP trial in patients with HCC and demonstrate a consistent clinical benefit regardless of HCV status. Although sorafenib is approved in the USA for the treatment of all unresectable advanced HCC based on the trials above, the results need to be interpreted with caution. In both trials, patients recruited were CP Class A and had relatively good performance status. These patients were chosen as it was felt liver function impairment associated with CP Class B or Cmay potentially confound the results of the study.
Hence, the effect of sorafenib in patients with poor liver function or decompensated liver disease is still unclear. The study by Abou Alfa et al. suggests no difference in the tolerability of sorafenib in patients with CP Class A or B disease. Updated data from this trial suggests a similar pharmacokinetic and toxicity profile for CP Class A and B patients. 28 out of 137 patients had blood samples analyzed for pharmacokinetics. AUC and Cmax were comparable, as were incidence rates for all adverse events and serious adverse events. Elevated bilirubin in this analysis may be related to sorafenib inhibition of UGT1A1 activity. As expected, CP B patients did worse than CP A patients, with more frequent worsening of their liver cirrhosis. It was unclear, though, if this was drug related or due to underlying disease progression.
More data is needed to confirm the safety and efficacy of sorafenib in CP B patients. Pinter et al. also reported a retrospective series evaluating sorafenib in 59 patients, 40 of whom had CP Class B disease and 17 CP Class C disease. The median survival times for these patients with CP Class A, B, and C disease were 8.3, 4.3, and 1.5 months, respectively, leading the authors to conclude that there was no benefit from systemic targeted therapy in patients with very advanced HCC. A phase I and pharmacokinetic study suggested that sorafenib doses should be titrated ag